Bulk optode-based ion selective optical sensors work on the basis of extraction equilibria, and their response toward the analyte ion is known to dependent on the sample pH. This pH dependence has been one of the major disadvantages that have hampered the broad acceptance of bulk optodes in chemical sensing. We present here for the first time the use of exhaustive Ca(2+)-selective nanosensors that may overcome this pH dependent response. The nanosensors were characterized at different pH and the same linear calibration was obtained in the Ca(2+) concentration range from 10(-7) M to 10(-5) M.

Ion selective optical sensors are typically interrogated under conditions where the sample concentration is not altered during measurement. We describe here an alternative exhaustive detection mode for ion selective optical sensors. This exhaustive sensor concept is demonstrated with ionophore-based nanooptodes either selective for calcium or the polycationic heparin antidote protamine. In agreement with a theoretical treatment presented here, linear calibration curves were obtained in the exhaustive detection mode instead of the sigmoidal curves for equilibrium-based sensors. The response range can be tuned by adjusting the nanosensor loading. The nanosensors showed average diameters of below 100 nm and the sensor response was found to be dramatically faster than that for film-based optodes. Due to the strong binding affinity of the exhaustive nanosensors, total calcium concentration in human blood plasma was successfully determined. Optical determination of protamine in human blood plasma using the exhaustive nanosensors was attempted, but was found to be less successful.

The sensing mechanism of fluorescent ion-selective nanosensors incorporating solvatochromic dyes (SDs), with K as model ion, is shown to change as a function of dye lipophilicity. Water-soluble SDs obey bulk partitioning principles where the sensor response directly depends on the lipophilicity of the SD and exhibits an influence on the phase volume ratio of nanosensors to aqueous solution (dilution effect). A lipophilization of the SDs is shown to overcome these limitations. An interfacial accumulation mechanism is proposed and confirmed with Förster resonance energy transfer (FRET) with a ratiometric near-infrared fluorescence FRET pair. This work lays the foundation for operationally more robust ion-selective nanosensors incorporating SDs.

Complexometric titrations rely on a drastic change of the pM value at the equivalence point with a water soluble chelator forming typically 1 : 1 complexes of high stability. The available chemical toolbox of suitable chelating compounds is unfortunately limited because many promising complexing agents are not water soluble. We introduce here a novel class of complexometric titration reagents, a suspension of polymeric nanospheres whose hydrophobic core is doped with lipophilic ion-exchanger and a selective complexing agent (ionophore). The emulsified nanospheres behave on the basis of heterogeneous ion exchange equilibria where the initial counter ion of the ion-exchanger is readily displaced from the emulsion for the target ion that forms a stable complex in the nanosphere core. Two different examples are shown with Ca(2+) and Pb(2+) as target ions. The lack of protonatable groups on the calcium receptor allows one to perform Ca(2+) titration without pH control.

Hydrogel is a unique family of biocompatible materials with growing applications in chemical and biological sensors. During the past few decades, various hydrogel-based optical ion sensors have been developed aiming at point-of-care testing and environmental monitoring. In this Perspective, we provide an overview of the research field including topics such as photonic crystals, DNAzyme cross-linked hydrogels, ionophore-based ion sensing hydrogels, and fluoroionophore-based optodes. As the different sensing principles are summarized, each strategy offers its advantages and limitations. In a nutshell, developing optical ion sensing hydrogels is still in the early stage with many opportunities lying ahead, especially with challenges in selectivity, assay time, detection limit, and usability.